The invention concerns a control reagent system for an analytical element, for example in the form of a test strip and, in particular, a test strip for determining a coagulation parameter which allows a differentiation between functioning analytical elements and non-functioning analytical elements. The invention also concerns corresponding analytical elements and methods for their control.
So-called carrier-bound tests are being used to an increasing extent for the qualitative and quantitative analysis of components of a liquid sample in particular a body fluid from humans or animals. Analytical elements (also referred to as test elements) are used for this where at least one reagent is embedded in a test field consisting of one or more layers, which is brought into contact with the sample. The reaction of sample and reagent results in a change in the analytical element that can be evaluated visually or with the aid of an instrument (usually by reflection photometry or electro-chemically). After a test has been carried out the used analytical element is disposed of.
Numerous different types of analytical element are known which differ in their measuring principle (e.g., optical or electrochemical) and the reagents that are used and in their construction and in particular with regard to the arrangement and attachment of the test layers. Strip-shaped analytical elements are of particular practical importance. These analytical elements that are also referred to as test strips are essentially composed of an elongate support layer made of a plastic material on which one or more test fields are attached.
The analytical elements are packaged in primary packaging in the interior of which they are stored until use i.e., until they are removed by the user and a test has been carried out with subsequent disposal. The analytical elements may be packaged individually in their own primary packaging. Analytical element packaging units are commonly used in which a plurality of analytical elements are located in the interior of a common primary packaging. The primary packaging usually contains a desiccant.
The interior of the primary packaging is usually substantially hermetically sealed. Hence, the storage conditions are essentially determined by the environmental conditions in the primary packaging during storage.
Many analytical elements contain reagents which can be damaged by certain storage conditions e.g., temperature, humidity, oxygen, light, etc., which makes them unusable for carrying out a reliable test. Hence, in order to avoid damage it is necessary to store the analytical element packaging unit under certain appropriate conditions recommended by the manufacturer. On the part of the manufacturer, the storage life of the analytical element is guaranteed for a certain period when stored properly.
The use of an analytical element with a damaged reagent can lead to a false test result which may result in a serious misinterpretation of, for example, the state of health of a person. Hence, in the past, various attempts have been made to reduce the risk of using analytical elements with storage damage.
For example, test reagents have been developed that are relatively insensitive to external effects. The aim of another development is to use elaborate primary packaging to minimize external effects on the reagents of the analytical elements. Both solutions are associated with substantially increased manufacturing costs. For safety reasons a relatively short shelf life is stated. As a result, analytical elements can no longer be used after the shelf life date has expired although it is not possible to check whether in fact there have been conditions which could have resulted in damage to the reagents.
Test strips for diagnostic blood examinations are subject to an extensive quality control before sale. Suitable shipping and storage conditions are intensively examined before they are launched on the market and are, for example, described on the packaging or in the package insert. Nevertheless, it cannot be completely excluded that strips are damaged before the expiration date during transport of the goods to the customer or due to incorrect storage by the customer and that there is a risk that false measurements are obtained when they are used.
Improper transport and/or storage conditions can be discovered by measurements using liquid controls which are distributed as additional system components besides the instrument and strips for most so-called point of care systems (PoC systems) that are used decentrally (i.e., outside of special laboratories i.e., for example, in doctor's offices, pharmacies or by the patient at home). Disadvantages of using liquid controls for PoC systems (e.g., for coagulation measurement systems) are their somewhat complicated handling, the costs for using usually two test strips and two control liquids (level 1 & level 2 control) and the fact that although usually strips from the same production lot and packaging are measured with the controls they are, however, inevitably other strips than those with which the blood sample of a patient is in fact examined.
These disadvantages are avoided by an on-board control (abbreviated as OBC in the following) which is integrated into each test strip and does not require an additional test liquid. Systems with on-board controls require no control liquids but work with the same sample liquid from which the parameter to be determined is determined with the measurement system.
A common feature of systems with on-board controls known in the art is that a blood sample is taken up into an analytical element through a capillary channel and is transported by capillary forces to a site of examination within the analytical element. The sample is divided by one or more branches of the capillary system and conveyed into one or more side channels. Reagents are then located in these side channels which constitute the actual OBC.
A common disadvantage of these on-board controls is that the test strips—in addition to the actual measurement channel for the patient sample—require several (usually two) additional channels. After being filled with the same patient blood, measurements are carried out in these additional channels which should give information about the integrity of the strip. This concept results in high manufacturing costs since the individual channels have to be separately provided with different reagents. Furthermore, such control systems require comparatively large sample volumes since, in addition to the actual measurement channel, at least one and usually even several control channels have to be filled with sample. Large sample volumes are regarded as being a particular disadvantage where patients themselves have to regularly obtain the sample i.e., for example, in so-called home monitoring especially in the case of diabetics or patients which have to monitor their own coagulation values since the collection of blood samples by puncturing the skin is painful and even more painful the more blood sample is required. Moreover, multichannel on-board control systems suffer from difficult filling mechanisms since the sample has to automatically penetrate into several channels and fill them.